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Development and Evaluation of Transferrin-Stabilized Paclitaxel Nanocrystal Formulation

By Ying Lu, Zhao-hui Wang, Tonglei Li, Helen McNally, Kinam Park and Michael Sturek

Abstract

The aim of the present study was to prepare and evaluate a paclitaxel nanocrystal-based formulation stabilized by serum protein transferrin in a non-covalent manner. The pure paclitaxel nanocrystals were first prepared using an antisolvent precipitation method augmented by sonication. The serum protein transferrin was selected for use after evaluating the stabilizing effect of several serum proteins including albumin and immunoglobulin G. The formulation contained approximately 55~60% drug and was stable for at least 3 months at 4 °C. In vivo antitumor efficacy studies using mice inoculated with KB cells demonstrate significantly higher tumor inhibition rate of 45.1% for paclitaxel-transferrin formulation compared to 28.8% for paclitaxel nanosuspension treatment alone. Interestingly, the Taxol® formulation showed higher antitumor activity than the paclitaxel-transferrin formulation, achieving a 93.3% tumor inhibition rate 12 days post initial dosing. However, the paclitaxel-transferrin formulation showed a lower level of toxicity, which is indicated by steady increase in body weight of mice over the treatment period. In comparison, treatment with Taxol® resulted in toxicity issues as body weight decreased. These results suggest the potential benefit of using a serum protein in a non-covalent manner in conjunction with paclitaxel nanocrystals as a promising drug delivery model for anticancer therapy

Topics: Antineoplastic Agents, chemistry, Nanoparticles, Taxoids, Transferrin, Paclitaxel, albumin, antitumor efficacy, Taxol, in vivo testing
Publisher: Elsevier
Year: 2014
DOI identifier: 10.1016/j.jconrel.2013.12.018
OAI identifier: oai:scholarworks.iupui.edu:1805/8229
Provided by: IUPUIScholarWorks
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